{"id":"doi:10.1038/s41467-026-78390-3","kind":"article","title":"Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer's disease from amyotrophic lateral sclerosis","authors":["Abu-Rumeileh S","Großkopf H","Guthknecht A","Mensch A","Osterloh D","Ratti A","Conrad J","Stapf C","Krippner J","Oeckl P","Stoltenburg-Didinger G","Maranzano A","Steinacker P","Weise CM","Barba L","D'Anna L","Klafki HW","Wiltfang J","Silani V","Froelich L","Ticozzi N","Hausner L","Thal DR","Weishaupt JH","Lachmann I"],"author_count":27,"year":2026,"published":"2026-10-22","venue":"Nature communications","cited_by":0,"doi":"10.1038/s41467-026-78390-3","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-026-78390-3","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-026-78390-3","updated":null,"pmid":"42918778","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Blood phosphorylated tau 217 (p-tau217) accurately detects Alzheimer's disease (AD) pathology but is also elevated in amyotrophic lateral sclerosis (ALS), likely reflecting peripheral (big) tau released from muscle. Assays selectively measuring brain-derived (BD-) tau and BD-p-tau217 are therefore needed. We analysed serum BD-tau and p-tau217 in ALS (n = 139), AD (n = 101) and controls (n = 75) using direct immunoassays and after BD-Tau immunoprecipitation (BD-Tau-IP), and tau species in brain (n = 16), spinal cord (n = 11) and muscle (n = 10) by targeted mass spectrometry. With the direct immunoassays, BD-tau and p-tau217 were increased in AD and ALS versus controls. After BD-Tau-IP, BD-tau and BD-p-tau217 were elevated in AD only, improving diagnostic accuracy. Mass spectrometry revealed a central-to-peripheral shift from BD-tau to big tau predominance, with exclusively big p-tau217 detected in muscle. Selective detection of BD-tau species improves the specificity of blood AD biomarkers by reducing peripheral tau confounding.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer's disease from amyotrophic lateral sclerosis\" by Abu-Rumeileh S, Großkopf H, Guthknecht A et al., https://doi.org/10.1038/s41467-026-78390-3, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}